Methamphetamine (meth) abuse in the U.S. has reached epidemic proportions, especially in the Western States and has been linked to a host of physical and psychological problems. Even more troubling, meth use during the adolescent period may interfere with normal brain development. These findings suggest that the endemic use of meth will require the development and testing of effective treatments aimed at adolescent abusers to forestall potentially deleterious outcomes. Moreover, combining clinical and neuroscientific approaches in an interdisciplinary model should lead to more prescriptive and efficacious treatments. In the current study, therefore, we merge the development of meth-specific interventions with a more detailed examination of how meth use affects neural systems and how alterations in specific brain areas influence treatment response. The proposed study represents a Stage IA/IB treatment development project, utilizing an interdisciplinary approach, consistent with the NIH Roadmap and designed to develop, refine, and pilot test a theoretically grounded intervention for adolescent meth abuse or dependence. The meth-specific intervention (AMT) will integrate family therapy with core elements of effective adult meth treatment programs, adapted to be developmentally appropriate for adolescents. This will be compared to a stand-alone family therapy intervention (FFT), an efficacious and effective treatment for adolescent substance use disorders. Further, in an effort to inform our treatment approach, a laboratory task will be developed to measure decision-making (i.e., risk-taking and impulsivity) and combined with functional brain imaging procedures (fMRI) to assess the effect of meth and other drug use on the neural circuits underlying these cognitive functions. Our Stage 1A research aim is to develop and test the meth-specific manualized treatment protocol. As well, we will examine the validity of our fMRI procedures in assessing the function of reward-related pathways in the brain known to be affected by meth in a subset of 32 adolescents referred for meth treatment and 16 nondrug-using controls to determine if the brain structures underlying decision-making in the two groups differ significantly. Stage 1B aims following will pilot test the manualized AMT procedure to establish its feasibility and validate its discriminability from FFT, verify the acceptability of the treatment by examining rates of engagement and retention, determine significant clinical outcomes relative to FFT alone, and examine predicted mediators and moderators to determine the core mechanisms of treatment efficacy. fMRI measures will be viewed relative to informing treatment engagement and retention as well as both short-term and long-term treatment outcomes. Stage 1B research will involve 60 adolescent meth abusers randomly assigned to either AMT or FFT who will be assessed at pretreatment, and at 3- months and 6-months following treatment initiation. The ultimate purpose of the research is to evaluate the potential promise of the AMT intervention, as informed by fMRI technology, for further investigation in a formal Stage 2 clinical trial.